A. Fatigue of single frog muscle fibers appeared as a decline in tension output during prolonged tetanic stimulation. The concentration of ATP (energy source for contraction) remained normal in fatigued fibers. Furthermore, ATP was not sequestered or unavailable for contraction. Fatigue therefore was due to an inability of the muscle to use energy in the form of ATP. We suggest that H ion, as lactic acid, accumulated in these fibers so as to interfere with excitaton-contraction coupling. B. The 14C-2-deoxy-D-glucose method, which was developed to measure regional cerebral metabolism, was extended in this study the analyze regional metabolism in the quadriceps femoris muscle of the rat. Stimulation of the femoral nerve at different frequencies produced different patterns of increased metabolism. The basis of these patterns remains to be determined. C. The perineurial sheath which surrounds peripheral nerve axons may regulate nerve function and development. Perineural permeability was measured for the first time (to 14C-sucrose) and was found to be very low, supporting a regulatory role for the sheath. Permeability was increase by stretch and by soaking in hypertonic solutions.